Complement system component 3 deficiency modulates the phenotypic profile of murine macrophages

IF 3.7 4区 医学 Q2 CELL BIOLOGY Cellular immunology Pub Date : 2024-10-22 DOI:10.1016/j.cellimm.2024.104886
Tiago Francisco da Silva , Thaís Akemi Amamura , Iuri Cordeiro Valadão , Milena Carvalho Carneiro , Vanessa Morais Freitas , Ana Paula Lepique , Lourdes Isaac
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Abstract

The Complement System is composed of more than 40 proteins that act in innate and adaptive immunity. C3 is the most abundant one and C3-deficient patients are more susceptible to recurrent and severe infections. Several studies have demonstrated the importance of C3 in controlling infections. However, its role in leukocyte biology is still poorly understood. This study aimed to evaluate several cellular parameters in macrophages from C3-deficient mice and compare them to similar cells from wild-type counterparts. We observed that in the absence of C3, the population of F4/80low macrophages in the peritoneal cavity of thioglycolate-treated mice is diminished, probably due to the lack of chemotactic factors like C3a and low levels of C5a. Using fluorescence microscopy analysis, we observed that macrophages from C3-deficient mice exhibited morphological alterations when compared to similar cells from wild-type mice. We observed a significant increase in the expression of CD11c, which is part of CR4 (CD11c/CD18), in macrophages from C3-deficient compared to cells from wild-type mice. Treatment with 12-o-tetradecanoylphorbol-13-acetate, stimulated ROS production and MAPK activation by macrophages. However, these parameters were lower in macrophages from C3-deficient mice when compared to wild-type counterparts. In addition, the phagocytosis of iC3b-opsonized Zymosan particles was diminished in macrophages from C3-deficient mice. Our results suggest that C3 deficiency in C57Black/6 mice may influence specific morphological and functional parameters of macrophages, cells of fundamental importance for both the innate and acquired immune responses.

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补体系统成分 3 缺乏可调节小鼠巨噬细胞的表型特征
补体系统由 40 多种蛋白质组成,在先天性免疫和适应性免疫中发挥作用。C3 是其中含量最高的一种,缺乏 C3 的患者更容易反复发生严重感染。多项研究证明了 C3 在控制感染方面的重要性。然而,人们对其在白细胞生物学中的作用仍知之甚少。本研究旨在评估 C3 缺乏小鼠巨噬细胞的几个细胞参数,并将其与野生型小鼠的类似细胞进行比较。我们观察到,在缺乏 C3 的情况下,巯基乙酸盐处理的小鼠腹腔中的低 F4/80 巨噬细胞数量会减少,这可能是由于缺乏 C3a 等趋化因子以及 C5a 水平较低的缘故。通过荧光显微镜分析,我们观察到 C3 缺陷小鼠的巨噬细胞与野生型小鼠的类似细胞相比发生了形态学改变。我们观察到,与野生型小鼠的细胞相比,C3缺陷小鼠巨噬细胞中作为CR4(CD11c/CD18)一部分的CD11c的表达明显增加。用 12-o-tetradecanoylphorbol-13-acetate 处理可刺激巨噬细胞产生 ROS 和激活 MAPK。然而,与野生型小鼠相比,C3缺陷小鼠的巨噬细胞中这些参数较低。此外,C3缺陷小鼠的巨噬细胞对iC3b-冲淡的Zymosan颗粒的吞噬能力也有所下降。我们的研究结果表明,C57Black/6小鼠的C3缺乏症可能会影响巨噬细胞的特定形态和功能参数,而巨噬细胞对先天性免疫反应和获得性免疫反应都至关重要。
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来源期刊
Cellular immunology
Cellular immunology 生物-免疫学
CiteScore
8.20
自引率
2.30%
发文量
102
审稿时长
30 days
期刊介绍: Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.
期刊最新文献
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